Asymmetric Synthesis of Phorboxazole B—Part I: Synthesis of the C20–C38 and C39–C46 Subunits
David A. Evans Prof.
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorVictor J. Cee
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorThomas E. Smith
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorDuke M. Fitch
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorPatricia S. Cho
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorDavid A. Evans Prof.
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorVictor J. Cee
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorThomas E. Smith
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorDuke M. Fitch
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorPatricia S. Cho
Department of Chemistry & Chemical Biology Harvard University Cambridge, MA 02138, USA, Fax: (+1) 617-495-1460
Search for more papers by this authorFinancial support was provided by the National Institutes of Health (GM-33328) and the National Science Foundation. An American Cancer Society Postdoctoral Fellowship to T.E.S. and an NSF Predoctoral Fellowship to V.J.C. are gratefully acknowledged. The NIH BRS Shared Instrumentation Grant Program 1-S10-RR04870 and the NSF (CHE 88-14019) are acknowledged for providing NMR facilities.
Abstract
Das antitumorwirksame marine Makrolid Phorboxazol B 1 wurde erstmals durch eine Totalsynthese hergestellt. Die Phorboxazole stehen stellvertretend für eine neue Strukturfamilie von Makroliden und gehören zu den cytostatisch wirksamsten Naturstoffen überhaupt: Sie hemmen das Wachstum von Tumorzellen bereits in nanomolaren Konzentrationen. Wichtige Kupplungen im Zuge der Synthese sind eine hochselektive, doppelt stereodifferenzierende Aldolreaktion, die Alkylierung eines metallierten Oxazols und eine durch einen Oxazolring begünstigte Wittig-Olefinierung. Nach der Makrocyclisierung wurde die noch fehlende Seitenkette durch eine hochselektive chelatkontrollierte Addition einer Alkenylmetallverbindung eingeführt.
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